HETEROCYCLIC AMINES, CYTOCHROME P4501A2, AND N-ACETYLTRANSFERASE - ISSUES INVOLVED IN INCORPORATING PUTATIVE GENETIC SUSCEPTIBILITY MARKERSINTO EPIDEMIOLOGIC STUDIES

PURPOSE: Heterocyclic amines (HCAs), which are found mainly in well-co oked meat, require metabolic activation to function as mutagens and an imal carcinogens. Enzymes such as cytochrome P4501A2 (CYP1A2) and N-ac etyltransferase (NAT2) perform this task and are subject to interindiv idual variation. The source of this variation may be genetic, as in th e case of NAT2, or both genetic and environmental as with CYP1A2. The present study examined the effect of HCAs on the NAT2 and CYP1A2 pheno types in 33 males and 33 females. METHODS: The subjects consumed a low HCA-containing dirt for 1 week followed by a high HCA diet for the su bsequent week. The subjects were phenotyped for CYP1A2 and NAT2 at the time of entry into the study (free-living), 1 week later (end of low- HCA or low-induction diet) and 2 weeks later (end of high-HCA or high- induction diet). RESULTS: Consistent with genetic sources oi variabili ty, NAT2 showed little effect of a high-HCA diet and exhibited high in traindividual correlation. CYP1A2, in contrast, was induced by a high- HCA diet and exhibited a more modest intraindividual correlation. CONC LUSIONS: Incorporating putative genetic susceptibility makers in popul ation studies requires consideration of issues of induction and inhibi tion of metabolizing enzymes, and effects of covariates. Published by Elsevier Science Inc.